TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK...

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with unclear pathogenesis.
• Microglia, the brain's immune cells, are implicated in ASD pathogenesis.
• The role of TREM2 in regulating microglia function in ASD requires further investigation.

Purpose of the Study:

• To investigate the potential mechanism of TREM2 in regulating microglia function in a rat model of ASD.
• To explore TREM2's influence on synaptic development and microglia phenotype in ASD.

Main Methods:

• Established a rat model of ASD via prenatal valproic acid (VPA) exposure.
• Assessed behavioral symptoms, synaptic development, and microglia phenotype at PND 7 and PND 28.
• Utilized lentivirus and adenovirus for TREM2 interference and overexpression in primary microglia cultures.

Main Results:

• VPA exposure induced ASD core symptoms, altered synapse-related proteins, and promoted pro-inflammatory microglia polarization.
• TREM2 overexpression increased Gephyrin and promoted an anti-inflammatory microglia phenotype (decreased CD86, increased CD206).
• TREM2 interference increased p-P38 MAPK and decreased p-ELK-1 protein levels.

Conclusions:

• TREM2 exhibits a protective effect in the VPA-induced ASD model.
• This protection is mediated by inhibiting the P38 MAPK pathway.
• TREM2 promotes anti-inflammatory microglia polarization and improves neuronal synaptic development in ASD.